Regulation of human papillomavirus type 31 late promoter activation and genome amplification by protein kinase C

The life cycle of papillomaviruses is tightly linked to differentiation of host keratinocytes, but the mechanisms and cues by which life cycle events are tied to differentiation remain obscure. We have begun a systematic study of the differentiation-dependent life cycle of HPV31. A variety of signaling pathways have been implicated in controlling keratinocyte differentiation, especially the protein kinase C (PKC) pathway. We have used pharmacological inhibitors to determine that genome amplification and late transcription depend on specific PKC isoforms, and that transcription and replication are independently controlled. We found that tyrosine kinases are necessary for viral amplification but not viral transcription. These studies indicate that the PKC pathway is an important regulator of differentiation-dependent HPV31 replication and transcription.